Bedair Hany S, Karthikeyan Tharun, Quintero Andres, Li Yong, Huard Johnny
Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Am J Sports Med. 2008 Aug;36(8):1548-54. doi: 10.1177/0363546508315470. Epub 2008 Jun 11.
Several therapeutic agents have been shown to inhibit fibrosis and improve regeneration after injury in skeletal muscle by antagonizing transforming growth factor-beta1. Angiotensin receptor blockers have been shown to have a similar effect on transforming growth factor-beta1 in a variety of tissues.
Systemic treatment of animals after injury of skeletal muscle with an angiotensin receptor blocker may decrease fibrosis and improve regeneration, mainly through transforming growth factor-beta1 blockade, and can be used to improve skeletal muscle healing after injury.
Controlled laboratory study.
Forty mice underwent bilateral partial gastrocnemius lacerations. Mice were assigned randomly to a control group (tap water), a low-dose angiotensin receptor blocker group (losartan, 0.05 mg/mL), or a high-dose angiotensin receptor blocker group (0.5 mg/mL). The medication was dissolved in tap water and administered enterally. Mice were sacrificed 3 or 5 weeks after injury, and the lacerated muscles were examined histologically for muscle regeneration and fibrosis.
Compared with control mice at 3 and 5 weeks, angiotensin receptor blocker-treated mice exhibited a histologic dose-dependent improvement in muscle regeneration and a measurable reduction in fibrous tissue formation within the area of injury.
By modulating the response to local and systemic angiotensin II, angiotensin receptor blocker therapy significantly reduced fibrosis and led to an increase in the number of regenerating myofibers in acutely injured skeletal muscle. The clinical implications for this application of angiotensin receptor blockers are potentially far-reaching and include not only sports- and military-related injuries, but also diseases such as the muscular dystrophies and trauma- and surgery-related injury.
Angiotensin receptor blockers may provide a safe, clinically available treatment for improving healing after skeletal muscle injury.
已有数种治疗药物通过拮抗转化生长因子-β1显示出可抑制骨骼肌损伤后的纤维化并促进再生。血管紧张素受体阻滞剂已被证明在多种组织中对转化生长因子-β1有类似作用。
骨骼肌损伤后用血管紧张素受体阻滞剂对动物进行全身治疗可能会减少纤维化并促进再生，主要是通过阻断转化生长因子-β1实现，且可用于改善损伤后骨骼肌的愈合。
对照实验室研究。
40只小鼠双侧腓肠肌部分撕裂。小鼠被随机分为对照组（自来水）、低剂量血管紧张素受体阻滞剂组（氯沙坦，0.05 mg/mL）或高剂量血管紧张素受体阻滞剂组（0.5 mg/mL）。药物溶解于自来水中经肠道给药。在损伤后3周或5周处死小鼠，对撕裂的肌肉进行组织学检查以评估肌肉再生和纤维化情况。
与损伤后3周和5周的对照小鼠相比，血管紧张素受体阻滞剂治疗的小鼠在肌肉再生方面呈现出组织学上的剂量依赖性改善，且损伤区域内纤维组织形成明显减少。
通过调节对局部和全身血管紧张素II的反应，血管紧张素受体阻滞剂治疗可显著减少急性损伤骨骼肌的纤维化，并使再生肌纤维数量增加。血管紧张素受体阻滞剂这种应用的临床意义可能影响深远，不仅包括与运动和军事相关的损伤，还包括诸如肌营养不良症以及与创伤和手术相关的损伤等疾病。
血管紧张素受体阻滞剂可能为改善骨骼肌损伤后的愈合提供一种安全、临床可用的治疗方法。
